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Trial record 19 of 793 for:    LENALIDOMIDE AND cells

Clinical Trial to Determinate Dose, Security and Efficacy or Lenalidomide and Rituximab (LR)-ESHAP in Patients With Diffuse Large B-cell Lymphoma

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ClinicalTrials.gov Identifier: NCT02340936
Recruitment Status : Completed
First Posted : January 19, 2015
Last Update Posted : February 21, 2019
Sponsor:
Collaborators:
Celgene Corporation
Dynamic Science S.L.
Thermo Fisher Scientific
Information provided by (Responsible Party):
Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea

Brief Summary:
The purpose of the Phase I of the study is to evaluate the safety and the maximum-tolerated dose (MTD) of the combination R-ESHAP with lenalidomide as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma The purpose of the Phase II of the study is to evaluate ORR of LR-ESHAP in patients with relapsed or refractory DLBCL candidates to HDT and ASCT

Condition or disease Intervention/treatment Phase
Diffuse Large B-cell Lymphoma Drug: LR-ESHAP (lenalidomide 5 mg) Drug: LR-ESHAP (lenalidomide 10 mg) Drug: LR-ESHAP (lenalidomide 15 mg) Drug: LR-ESHAP (lenalidomide 20 mg) Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 53 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: National, Open-label, Multicentre Phase I-II Study of Combination R-ESHAP With Lenalidomide as Salvage Therapy for Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma Candidates to Stem-cell Transplantation
Actual Study Start Date : January 2011
Actual Primary Completion Date : September 2016
Actual Study Completion Date : February 20, 2019


Arm Intervention/treatment
Experimental: LR-ESHAP (lenalidomide 5 mg)
Intervention: lenalidome 5mg combined with R-ESHAP (3 cycles of treatment every 21 days: lenalidomide 5 mg/day (day 1 to 14 except cycle 2 that will be administered from day 1 to 10), etoposide 40 mg/m2/day (day 1 to day 4), methylprednisolone 500 mg/day (day 1 to day 5), cisplatin 25 mg/m2/day (day 1 to day 4), cytarabine 2000 mg/m2 (day 5) and rituximab 375 mg/m2 (day 1 or 5)).
Drug: LR-ESHAP (lenalidomide 5 mg)
3 cycles of lenalidomide 5mg, etoposide, methylprednisolone, cisplatin, cytarabine and rituximab every 3 weeks.
Other Name: LR-ESHAP

Experimental: LR-ESHAP (lenalidomide 10mg)
Intervention: lenalidome 10mg combined with R-ESHAP( 3 cycles of treatment every 21 days: lenalidomide 10 mg/day (day 1 to 14 except cycle 2 that will be administered from day 1 to 10), etoposide 40 mg/m2/day (day 1 to day 4), methylprednisolone 500 mg/day (day 1 to day 5), cisplatin 25 mg/m2/day (day 1 to day 4), cytarabine 2000 mg/m2 (day 5) and rituximab 375 mg/m2 (day 1 or 5)).
Drug: LR-ESHAP (lenalidomide 10 mg)
3 cycles of lenalidomide 10mg, etoposide, methylprednisolone, cisplatin, cytarabine and rituximab every 3 weeks.
Other Name: LR-ESHAP

Experimental: LR-ESHAP (lenalidomide 15mg)
Intervention: lenalidome 15mg combined with R-ESHAP (3 cycles of treatment every 21 days: lenalidomide 15 mg/day (day 1 to 14 except cycle 2 that will be administered from day 1 to 10), etoposide 40 mg/m2/day (day 1 to day 4), methylprednisolone 500 mg/day (day 1 to day 5), cisplatin 25 mg/m2/day (day 1 to day 4), cytarabine 2000 mg/m2 (day 5) and rituximab 375 mg/m2 (day 1 or 5)).
Drug: LR-ESHAP (lenalidomide 15 mg)
3 cycles of lenalidomide 15mg, etoposide, methylprednisolone, cisplatin, cytarabine and rituximab every 3 weeks.
Other Name: LR-ESHAP

Experimental: LR-ESHAP (lenalidomide 20mg)
Intervention: lenalidome 20mg combined with R-ESHAP (3 cycles of treatment every 21 days: lenalidomide 20 mg/day (day 1 to 14 except cycle 2 that will be administered from day 1 to 10), etoposide 40 mg/m2/day (day 1 to day 4), methylprednisolone 500 mg/day (day 1 to day 5), cisplatin 25 mg/m2/day (day 1 to day 4), cytarabine 2000 mg/m2 (day 5) and rituximab 375 mg/m2 (day 1 or 5)).
Drug: LR-ESHAP (lenalidomide 20 mg)
3 cycles of lenalidomide 20mg, etoposide, methylprednisolone, cisplatin, cytarabine and rituximab every 3 weeks.
Other Name: LR-ESHAP




Primary Outcome Measures :
  1. Phase I of the study: to evaluate the safety and the maximum-tolerated dose (MTD) of the combination R-ESHAP with lenalidomide as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma (determine maximum tolerated dose) [ Time Frame: During 3 cycles of treatment (2 months after the initiation of study treatment) ]
    To determine the MTD of the combination R-ESHAP with lenalidomide

  2. Phase II of the study: Phase II: to evaluate ORR of LR-ESHAP in patients with relapsed or refractory DLBCL candidates to HDT and ASCT (determine the overall response rate) [ Time Frame: After 3 cycles of treatment (2 months after the initiation of study treatment) ]
    To determine the overall response rate of LR-ESHAP


Secondary Outcome Measures :
  1. Phase I of the study: to analyze the adverse events of LR-ESHAP (frequency and severity of the adverse events) [ Time Frame: During study treatment period (3 cycles of LR-ESHAP and ASCT) until end of treatment visit (3 months after ASCT) ]
    To describe the frequency and severity of the adverse events observed with LR-ESHAP regimen

  2. Phase I of the study: preliminarily analyze effectiveness (response rates (CR and PR), duration of response and survival (DFS and OS) [ Time Frame: After 3 cycles of treatment (two months after the initiation of the study treatment) and during follow-up period (36 months) ]
    To determine response rates (CR and PR), duration of response and survival (DFS and OS)

  3. Phase I of the study: evaluate haematopoietic progenitor cells mobilization after treatment with LR-ESHAP (Evaluate CD34+ cell count) [ Time Frame: After cycle 2 (5 weeks after the initiation of study treatment) or cycle 3 (9 weeks after the initiation of study treatment) ]
    Evaluate CD34+ cell count after treatment with LR-ESHAP

  4. Phase I of the study: evaluate hematologic recovery after HSCT (recovery of blood parameters) [ Time Frame: After HSCT (between 5 and 8 weeks after the initiation of the cycle 3 of treatment) ]
    To evaluate the recovery of blood parameters after HSCT

  5. Phase II of the study: analyze effectiveness (Complete remission (CR) rate (determined by positron emission tomography [PET]/CT), event-free survival (EFS) and overall survival (OS) [ Time Frame: After 3 cycles of treatment (2 months after the initiation of the study treatment) and during follo-up period (36 months) ]
    Complete remission (CR) rate (determined by positron emission tomography [PET]/CT), event-free survival (EFS) and overall survival (OS).

  6. Phase II of the study: rate of transplanted patients (number of patients that undergo HSCT) [ Time Frame: 6-8 weeks aftter the initiation of cycle 3 ]
    To determine the number of patients that undergo HSCT

  7. Phase II of the study: to analyze the adverse events of LR-ESHAP and ASCT. (frequency and severity of the adverse events) [ Time Frame: During study treatment period (3 cycles of LR-ESHAP and ASCT) until end of treatment visit (3 months after ASCT) ]
    To describe the frequency and severity of the adverse events observed with LR-ESHAP regimen and ASCT

  8. Phase II of the study: evaluate mobilization after treatment with LR-ESHAP (number of stem cells (2 x 106/Kg Hematopoietic progenitor cell antigen (CD34)+ cells) collected after the salvage therapy.) [ Time Frame: After cycle 2 (5 weeks after the initiation of study treatment) or cycle 3 (9 weeks after the initiation of study treatment) ]
    number of stem cells (2 x 106/Kg CD34+ cells) collected after the salvage therapy.

  9. Phase II of the study: influence of clinical and biological prognostic factors on response rates and survival (influence of clinical and biological (such as cell of origin) prognostic factors on response rates and survival.) [ Time Frame: During study treatment (2 months) until end of treatment visit (3 months after ASCT) and during follow-up period (36 months) ]
    Influence of clinical and biological (such as cell of origin) prognostic factors on response rates and survival.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. The patient must, at the investigator's opinion, be able to meet all requirements of the clinical trial.
  2. Patients must give voluntarily informed consent before performing any test test that is not part of routine care of patients.
  3. Age between 18 and 70 years.
  4. Candidate for treatment with high-dose QT and HSCT .
  5. Diffuse large B-cell lymphoma (LDCGB) histological diagnosis according to the WHO classification ( see Annex 8).
  6. Refractory lymphoma or relapsed after 1st line treatment consisting of rituximab combined with a regimen of chemotherapy (CT scan ) including anthracyclines. :

    Relapse is defined as recurrence of lymphoma after obtaining complete response (RC) with 1st line treatment . In these cases, LDCGB histologic confirmation at the time of relapse is recommended

    Refractory lymphoma be considered if it meets one of the following criteria :

    partial response after at least 6 cycles of 1st line regimen . They may also include patients in partial response after 4 cycles if the researcher believes that the response is suboptimal, and patients with stage I- II if they have received 3 cycles of R- QT + affection field radiotherapy .

    stable disease after at least 3 cycles of 1st line regimen . progression during treatment of 1st line , defined as response criteria for malignant lymphoma 2007 (see Annex 9)

  7. CT scan evidence of at least two clearly demarcated lesions with a diameter of 1.5 cm, or 1 well-defined lesion with a diameter > 2 cm .
  8. Evidence of positive lesions by PET, coincident with the anatomical areas affected by CT scan .
  9. Eastern cooperative oncology group performance status (ECOG) less than or equal to 2.
  10. Resolution of toxicities caused by the 1st line regimen to less than or equal to grade 1.
  11. Women of childbearing age ( see Appendix 12) must: Obtain a negative pregnancy test before starting medically supervised therapy study. Must accept continuing pregnancy tests conducted during the course of the study and after the end of study therapy . This applies even if the patient practices complete and continued abstinence .

They must either commit to continued abstinence or heterosexual sex (which should be reviewed monthly ) or agree to use and be capable of complying with effective contraception without interruption, 28 days before starting the study drug during the study therapy (including during periods of dose interruptions ) , and for 28 days after discontinuation of study therapy .

12 male patients ( see Appendix 12) must:

  • Accept to use a latex condom during any sexual relations with women of childbearing potential , even if they have had a vasectomy , while participating in this study, during dose interruptions and after discontinuation of treatment .
  • Accept refrain from donating sperm while participating in this study and for a time after cessation of treatment (see specific data ) . 13. All patients must: Understand that the study drug could potentially have a teratogenic risk . Agree to abstain from donating blood while they are taking the treatment and after discontinuation of study drug therapy .

Agree not to share study medication with anyone else. For advice on precautions against pregnancy and potential risks of fetal exposure

Exclusion Criteria:

1. Patients that previously received any antitumor agent for the treatment of LDCGB except : I ) rituximab in combination with regimen including anthracyclines II ) radiotherapy as part of first-line treatment .

2 Previously received any of the following treatments in the 28 days prior to the test regime : I ) antitumor chemotherapeutic agents ; II ) radiotherapy , unless limited to a maximum dose of < or =10 Gy to control severe life-threatening symptoms ; III ) glucocorticoid except equivalent doses < or = 1 mg / kg of prednisolone / day with duration < or = 7 days; iv ) any therapeutic agent under investigation.

3. Known involvement of the central nervous system (CNS) by lymphoma. 4. Presence of abnormal or clinically significant cardiac disease, such as acute myocardial infarction or unstable angina within 6 months prior to initiation of treatment with LR- ESHAP , grade III or IV heart failure, uncontrolled hypertension or history of poor compliance with antihypertensive treatment , uncontrolled treated arrhythmias, except , with the exception of extra systoles or minor conduction abnormalities.

5. Any other serious or uncontrolled medical condition , such as diabetes, uncontrolled active infection, significant cerebrovascular disease, poorly controlled psychiatric disease, etc. .

6. Known or suspected hypersensitivity to any of the agents of the treatment under evaluation.

7. Presence of any limitations that compromise the patient's ability to comply with treatment .

8. Positive serology for HIV or Hepatitis B Virus (HBV) surface antigen (HBsAg ) . If negative for HBsAg but HBcAb positive and HBsAb negative, a HB DNA test will be performed and if positive the subject will be excluded. Note: If HBcAb positive and HBsAb positive, which is indicative of a past infection, the subject can be included 9. Active Hepatitis C (RNA positive serum) . If RNA positive result would exclude the patient from the trial in cases of patients with positive serology for Hepatitis C Virus (HCV). If the load ( RNA ) were HCV negative patients could be included in the study.

10. Prior history of malignancy other than to LDCGB (except basal or squamous cell skin and in situ carcinoma of the cervix or breast ) unless the patient free of disease beyond 5 years are.

11 Changes in laboratory values ??that might involve unacceptable risks or compromise compliance with the protocol , including: platelets < 50 x 109 / L or neutrophils <1 x 109 / L , unless attributed to infiltration by lymphoma bone marrow (MO) .

or creatinine > 1.5 times the normal upper limit . or Total bilirubin > 2 times the upper limit of normal or alanine aminotransferase (ALT) > 2.5 times the normal upper limit or alkaline phosphatase > 2.5 times the normal upper limit , unless it is attributed to hepatic infiltration by lymphoma.

12. Pregnant or breast-feeding. 13. Females of childbearing potential who do not agree to undergo pregnancy tests or repeated use effective birth control while included in the clinical trial.

14. Males patients (whose sexual partners are women of childbearing potential ) that not accept use effective birth control methods while included in the clinical trial.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02340936


Locations
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Spain
ICO- Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, Spain, 08916
ICO- Hospital Duran i Reynals
L´Hospitalet de Llobregat, Barcelona, Spain, 08908
Hospital del Mar
Barcelona, Spain, 08003
Hospital Clinic i Provincial de Barcelona
Barcelona, Spain, 08036
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041
Hospital Regional Universitario de Málaga
Málaga, Spain, 29010
Alejandro Martín
Salamanca, Spain, 37007
Hospital Universitario Virgen del Rocío
Sevilla, Spain, 41013
Hospital Universitario La Fe
Valencia, Spain, 46026
Sponsors and Collaborators
Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
Celgene Corporation
Dynamic Science S.L.
Thermo Fisher Scientific
Investigators
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Principal Investigator: Alejandro Martin Hospital Universitario de Salamanca
Principal Investigator: Dolores Caballero Hospital Universitario de Salamanca

Additional Information:
Publications:

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Responsible Party: Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
ClinicalTrials.gov Identifier: NCT02340936     History of Changes
Other Study ID Numbers: LR-ESHAP
First Posted: January 19, 2015    Key Record Dates
Last Update Posted: February 21, 2019
Last Verified: February 2018
Additional relevant MeSH terms:
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Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lenalidomide
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cytarabine
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Cisplatin
Rituximab
Etoposide
Etoposide phosphate
Prednisolone hemisuccinate
Prednisolone phosphate
Antineoplastic Agents
Antineoplastic Agents, Immunological
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents